Upregulation of the mitochondrial Lon Protease allows adaptation to acute oxidative stress but dysregulation is associated with chronic stress, disease, and aging.
Upregulation of the mitochondrial Lon Protease allows adaptation to acute oxidative stress but dysregulation is associated with chronic stress, disease, and aging.
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DOI：
10.1016/j.redox.2013.01.015
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发表时间：
2013-02-09
期刊：
影响因子：
11.4
通讯作者：
Davies, Kelvin J. A.
中科院分区：
文献类型：
--
作者：
Ngo, Jenny K.;Pomatto, Laura C. D.;Davies, Kelvin J. A.
氧化修饰蛋白质的消除是维持细胞稳态的关键过程，特别是在应激期间。线粒体是蛋白质密集、高流量的隔间，其多肽不断暴露于超氧化物、过氧化氢和其他反应性物质，这些物质是由呼吸链的“电子泄漏”产生的。线粒体蛋白的氧化应激水平不是恒定的，而是随着许多代谢和环境因素而变化很大。氧化的线粒体蛋白质必须迅速去除（通过蛋白水解降解），否则它们会聚集、交联并导致毒性。Lon蛋白酶是线粒体基质内氧化蛋白降解的关键酶。在急性应激条件下，Lon是高度可诱导的，可能与氧化剂作为信号诱导剂，从而提供增加的保护。然而，在慢性压力条件下，Lon水平实际上会下降。Lon水平也随着年龄和衰老而下降，并且衰老细胞甚至在急性应激期间丧失诱导Lon的能力。我们建议，Lon的调节是双相的，因为它是上调在短暂的压力和下调在慢性压力和老化，我们认为，Lon的响应性的损失可能是一个重要的因素，在老化，并在与年龄有关的疾病。
The elimination of oxidatively modified proteins is a crucial process in maintaining cellular homeostasis, especially during stress. Mitochondria are protein-dense, high traffic compartments, whose polypeptides are constantly exposed to superoxide, hydrogen peroxide, and other reactive species, generated by ‘electron leakage’ from the respiratory chain. The level of oxidative stress to mitochondrial proteins is not constant, but instead varies greatly with numerous metabolic and environmental factors. Oxidized mitochondrial proteins must be removed rapidly (by proteolytic degradation) or they will aggregate, cross-link, and cause toxicity. The Lon Protease is a key enzyme in the degradation of oxidized proteins within the mitochondrial matrix. Under conditions of acute stress Lon is highly inducible, possibly with the oxidant acting as the signal inducer, thereby providing increased protection. It seems that under chronic stress conditions, however, Lon levels actually decline. Lon levels also decline with age and with senescence, and senescent cells even lose the ability to induce Lon during acute stress. We propose that the regulation of Lon is biphasic, in that it is up-regulated during transient stress and down-regulated during chronic stress and aging, and we suggest that the loss of Lon responsiveness may be a significant factor in aging, and in age-related diseases.
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影响因子：
2.9
作者：
Bulteau, AL;Ikeda-Saito, M;Szweda, LI
通讯作者：
Szweda, LI
DOI：
10.1046/j.1432-1033.2003.03598.x
发表时间：
2003-05-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Bakala, H;Delaval, E;Friguet, B
通讯作者：
Friguet, B
影响因子：
3.5
作者：
Chantrel-Groussard, K;Geromel, V;Rustin, P
通讯作者：
Rustin, P
影响因子：
168.9
作者：
Brinkman, K;Smeitink, JA;Reiss, P
通讯作者：
Reiss, P
影响因子：
3.5
作者：
Bota, DA;Van Remmen, H;Davies, KJA
通讯作者：
Davies, KJA